scholarly journals Protein Tyrosine Phosphatase-PEST and β8 Integrin Regulate Spatiotemporal Patterns of RhoGDI1 Activation in Migrating Cells

2015 ◽  
Vol 35 (8) ◽  
pp. 1401-1413 ◽  
Author(s):  
Hye Shin Lee ◽  
Mujeeburahiman Cheerathodi ◽  
Sankar P. Chaki ◽  
Steve B. Reyes ◽  
Yanhua Zheng ◽  
...  
Keyword(s):  
Cell Motility ◽  
Protein Tyrosine Phosphatase ◽  
Protein Complexes ◽  
Tyrosine Phosphatase ◽  
Leading Edge ◽  
Protein Tyrosine ◽  
Motile Cells ◽  
Signaling Events ◽  
Gdp Dissociation Inhibitor ◽  
Migrating Cells

Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor β8 integrin that plays essential roles in directional cell motility. β8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells.

scholarly journals Transforming Growth Factor β (TGF-β)-Smad Target Gene Protein Tyrosine Phosphatase Receptor Type Kappa Is Required for TGF-β Function

2005 ◽  
Vol 25 (11) ◽  
pp. 4703-4715 ◽  
Author(s):  
Shizhen Emily Wang ◽  
Frederick Y. Wu ◽  
Incheol Shin ◽  
Shimian Qu ◽  
Carlos L. Arteaga
Keyword(s):  
Rna Interference ◽  
Growth Factor ◽  
Cell Motility ◽  
Protein Tyrosine Phosphatase ◽  
Transforming Growth Factor ◽  
Tyrosine Phosphatase ◽  
Transforming Growth Factor Β ◽  
Receptor Type ◽  
Her2 Overexpression ◽  
Protein Tyrosine

ABSTRACT Transforming growth factor β (TGF-β) inhibits proliferation and promotes cell migration. In TGF-β-treated MCF10A mammary epithelial cells overexpressing HER2 and by chromatin immunoprecipitation, we identified novel Smad targets including protein tyrosine phosphatase receptor type kappa (PTPRK). TGF-β up-regulated PTPRK mRNA and RPTPκ (receptor type protein tyrosine phosphatase kappa, the protein product encoded by the PTPRK gene) protein in tumor and nontumor mammary cells; HER2 overexpression down-regulated its expression. RNA interference (RNAi) of PTPRK accelerated cell cycle progression, enhanced response to epidermal growth factor (EGF), and abrogated TGF-β-mediated antimitogenesis. Endogenous RPTPκ associated with EGF receptor and HER2, resulting in suppression of basal and ErbB ligand-induced proliferation and receptor phosphorylation. In MCF10A/HER2 cells, TGF-β enhanced cell motility, FAK phosphorylation, F-actin assembly, and focal adhesion formation and inhibited RhoA activity. These responses were abolished when RPTPκ was eliminated by RNA interference (RNAi). In cells expressing RPTPκ RNAi, phosphorylation of Src at Tyr527 was increased and (activating) phosphorylation of Src at Tyr416 was reduced. These data suggest that (i) RPTPκ positively regulates Src; (ii) HER2 signaling and TGF-β-induced RPTPκ converge at Src, providing an adequate input for activation of FAK and increased cell motility and adhesion; and (iii) RPTPκ is required for both the antiproliferative and the promigratory effects of TGF-β.

scholarly journals Regulation of the Src Kinase-associated Phosphoprotein 55 Homologue by the Protein Tyrosine Phosphatase PTP-PEST in the Control of Cell Motility

2013 ◽  
Vol 288 (36) ◽  
pp. 25739-25748 ◽  
Author(s):  
Emily Ayoub ◽  
Anita Hall ◽  
Adam M. Scott ◽  
Mélanie J. Chagnon ◽  
Géraldine Miquel ◽  
...  
Keyword(s):  
Cell Motility ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Src Kinase ◽  
Protein Tyrosine

scholarly journals Loss of the Protein-Tyrosine Phosphatase DEP-1/PTPRJ Drives Meningioma Cell Motility

2010 ◽  
Vol 21 (4) ◽  
pp. 405-418 ◽  
Author(s):  
Astrid Petermann ◽  
Daniela Haase ◽  
Andrea Wetzel ◽  
Kamal K. Balavenkatraman ◽  
Tencho Tenev ◽  
...  
Keyword(s):  
Cell Motility ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Meningioma Cell

Protein tyrosine phosphatase receptor–type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell–receptor signaling, and cellular proliferation

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3428-3433 ◽  
Author(s):  
Linfeng Chen ◽  
Przemyslaw Juszczynski ◽  
Kunihiko Takeyama ◽  
Ricardo C. T. Aguiar ◽  
Margaret A. Shipp
Keyword(s):  
B Cell ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Type ◽  
Protein Tyrosine ◽  
Downstream Signaling ◽  
Bcr Signaling ◽  
Signaling Events

Abstract The strength and duration of B-cell–receptor (BCR) signaling depends upon the balance between protein tyrosine kinase (PTK) activation and protein tyrosine phosphatase (PTP) inhibition. BCR-dependent activation of the SYK PTK initiates downstream signaling events and amplifies the original BCR signal. Although BCR-associated SYK phosphorylation is clearly regulated by PTPs, SYK has not been identified as a direct PTP substrate. Herein, we demonstrate that SYK is a major substrate of a tissue-specific and developmentally regulated PTP, PTP receptor–type O truncated (PTPROt). PTPROt is a member of the PTPRO family (also designated GLEPP, PTP-Ø, PTP-oc, and PTPu2), a group of highly conserved receptor-type PTPs that are thought to function as tumor suppressor genes. The overexpression of PTPROt inhibited BCR-triggered SYK tyrosyl phosphorylation, activation of the associated adaptor proteins SHC and BLNK, and downstream signaling events, including calcium mobilization and mitogen-activated protein kinase/extracellular signal–regulated kinase (MAPK/ERK) activation. PTPROt overexpression also inhibited lymphoma cell proliferation and induced apoptosis in the absence of BCR cross-linking, suggesting that the phosphatase modulates tonic BCR signaling.

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